An optically-active amino compound is a compound that is very useful as a synthetic intermediate for various medicines and pesticides.
A large number of methods for producing an optically-active amine compound with use of a transaminase, especially of methods for producing an optically-active α-amino acid, have been reported. An amination reaction catalyzed by a transaminase is a reversible reaction (equilibrium reaction). Therefore, in order to obtain a desired amine compound in good yield, it is necessary to bias the equilibrium reaction toward production of the desired amine compound. This is achieved, for example, by a method that involves the removal of a by-product compound from the reaction system. A number of such methods have been reported.
Examples of a method for producing an optically-active α-amino acid through amination of an α-keto acid with use of a transaminase are as follows:
(1) A method, using coupled aminotransferases, which biases equilibrium in reaction by removing a by-product α-keto acid (Patent Document 1: International Publication No. WO 87/01727 Pamphlet);
(2) A method, using an L-asparagine acid as an amino donor, which biases equilibrium in reaction by causing an acetolactate synthase to act on a pyruvic acid produced through chemical decarbonization of by-product oxaloacetate (Patent Document 2: Japanese Translation of PCT Patent Application Publication No. 514921/2002 (Tokuhyo 2002-514921));
(3) A method, using a D-amino acid as an amino donor, which biases equilibrium in reaction by causing an amino-acid dehydrogenase, an amino-acid racemase, and the like to act on a by-product α-keto acid to convert the α-keto acid into a D-amino acid serving as an amino donor (Patent Document 3: Japanese Examined Patent Application Publication No. 85718/1995 (Tokukohei 7-85718)); and
(4) A method, using DL-alanine as an amino donor, which biases equilibrium in reaction by causing a lactate dehydrogenase and an expensive NADH to act on a by-product pyruvic acid to convert the pyruvic acid into a lactic acid (Patent Document 4: International Publication No. WO 91/05870 Pamphlet).
The above methods (1) to (3) are also described in Trends biotechnol., 16, 412-418 (1998) (Non-patent Document 1).
Further, examples of a method for producing an optically-active amine compound other than an optically-active α-amino acid with use of a transaminase are as follows:
(a) A method, using a cell-free extract of microorganisms Vibrio fluvialis, which, during an amination reaction of acetophenone with use of L-alanine as an amino donor, biases equilibrium in reaction by causing a lactate dehydrogenase and an expensive NADH to act on a by-product pyruvic acid to convert the pyruvic acid into a lactic acid (Non-patent Document 2: Biotechnol. Bioeng., 65(2), 206-211 (1999)); and
(b) A method that, during production of (S)-methoxyisopropylamine with use of 2-aminopropane as an amino donor, biases equilibrium in reaction by removing by-product acetone from the reaction system through an increase in reaction temperature (Non-patent Document 3: Chimia, 53(12), 584-589 (1999)).
In Non-patent Document 2 described above in (a), the authors conclude that: A reaction that involves the conjugation of a lactate dehydrogenase to a cell-free extract requires an NADH regeneration system, and the addition of another enzyme complicates the reaction system; therefore, a reaction that involves the use of viable bacteria of Vibrio fluvialis is superior. Thus, the authors of Non-patent Document 2, who are skilled in the art, hold a negative view on a reaction that involves a combination of a transaminase, a lactate dehydrogenase, and a coenzyme regeneration system.
Patent Document 1: International Publication No. WO 87/01727 Pamphlet
Patent Document 2: Japanese Translation of PCT Patent Application Publication No. 514921/2002 (Tokuhyo 2002-514921)
Patent Document 3: Japanese Examined Patent Application Publication No. 85718/1995 (Tokukohei 7-85718)
Patent Document 4: International Publication No. WO 91/05870 Pamphlet
Non-patent Document 1: Trends biotechnol., 16, 412-418 (1998)
Non-patent Document 2: Biotechnol. Bioeng., 65(2), 206-211 (1999)
Non-patent Document 3: Chimia, 53(12), 584-589 (1999)